An ECG signal collected (i.e. sensed or detected) by external electrodes or an endocardiac probe present in a characteristic manner a series of wave complexes known as the “PQRST” complexes corresponding to the succession of the cardiac beats of the patient. On a cycle cardiac, the QRS, complex, which represents the repolarization of the ventricles, is followed by a wave known as the “T wave” or the “repolarization wave” (these two terms will be used interchangeably hereafter). It is the electric translation on the ECG of the repolarization of the myocardic cells of the ventricles. The T wave (repolarization wave) presents an amplitude and form (shape) that are quite variable, and is very sensitive to conduction disturbances in the myocardium.
Various devices have been specifically proposed to analyze the variability of the T wave, for example, the French Patent No. Fr-A-2 784 035 (commonly assigned herewith to Ela Médical), which analyzes the T wave to diagnose the appearance and then the evolution of an ischemic state in real time, so as to be able to adapt consequently the operation of the device. In this document, the device for the analysis of the T wave is a device incorporated in an implant, e.g., a cardiac pacemaker or cardiovertor and operative in real time, by analysis of the moment of arrival of the leading edge repolarisation wave.
Another parameter of the T wave that is known to be interesting to evaluate is the alternans, which is a very small repetitive pattern of the variability, on the order of millivolts, from one beat to the following beat, in the waveform of the ECG in the temporal segment corresponding to the repolarization wave. This variation pattern is of type ABABAB . . . , i.e., if one examines every other wave, these waves are very similar, but comparing one T wave to the immediately following T wave reveals a detectable variation of the amplitude, the level of which constitutes a significant indicator of a cardiac electric instability of the patient. The presence of a T wave alternans, indicative of a non uniform repolarization of the myocardium, is in particular a very good predictor of fibrillation, and thus of the clinical risk of ventricular arrhythmia and sudden death.
In the case of a implanted defibrillator with an integrated analyzer of the T wave alternans, as described for example in French Patent No. Fr-A-2 808 213 (Medtronic Inc), it is possible to provide quickly a warning to the patient or to the doctor in the event of risk of major cardiac risk, or to even start a therapy by the device when this risk is declared.
Independently of the implanted devices integrating an analyzer functioning in real time, it also is possible to monitor for the presence of a T wave alternans based upon signals collected by a so called “Holter” recorder, i.e., an apparatus that performs an essentially uninterrupted recording of cardiac activity signals collected by means of implanted electrodes or external electrodes over a long period. The examination of the Holter recording can in this instance include the search for a possible T wave alternans, constituting an indicator of risk. Such an analysis is considerably important in identifying those patients that are likely to benefit from the implantation of an implantable defibrillator/cardiovertor as a primary preventative measure.
The presence of a T wave alternans is also a significant predictor of a degradation of the ischemic state of the patient. Indeed, an ischemic state results in an quasi-instantaneous and detectable modification of the ventricular repolarization wave (the ischemia appears following a stop or a reduction of the blood irrigation of the heart).
The search for a T wave alternans until now has been relatively difficult because the cycle to cycle variation of the alternans is very small (typically a variation of about 5 μV), in particular when compared to the mean level of the noise present in ECG signal, which noise has a typical mean level of about 10 μV. The search for a T wave alternans thus requires the implementation of means which at the same time are very sensitive and have a noise good immunity (thus implying complex algorithms and filtering).
The algorithms proposed until now have required relatively significant means for calculation (bit resolution, computation power, memory, etc.) thus implying resources for performing the calculations that do not allow for implementation in a microcomputer or more particularly in an ambulatory or implanted apparatus (unless one is willing to tolerate excessive processing times and/or lower quality in the result). However, to obtain quickly a reliable predictor of fibrillation or ischemia of the myocardium, it is significant to be able to reveal and discriminate quickly a certain number of micro-variations, which can be very significant for obtaining a reliable and relevant diagnosis.
One known technique for analyzing a T wave alternans is the spectral method (see in particular U.S. Pat. No. 4,802,491 and Rosembaum D S et al., “Electrical Alternans and Vulnerability to Ventricular Arrhythmias,” N Engl J Med, 1994; 330: 235–241). This technique proposes to analyze the energy variations of the frequency spectrum of ECG signal, so as to seek a peak of energy for a revealing frequency of the required fluctuation.
Another known technique for analyzing a T wave alternans is the complex demodulation technique (U.S. Pat. No. 5,842,997 and Nearing B. et al., “Dynamic Tracking of Cardiac Vulnerability by Complex Demodulation of the T-Wave,” Science, 1991; 252: 437–440). This technique seeks to model the fluctuation of the amplitude of the T wave by a sinusoid of variable amplitude and variable phase, so as to ensure a dynamic follow-up of the variations of alternans of the T wave. Its intrinsic complexity, however, makes the method difficult to apply without addition of specific hardware circuits.
Another known technique for analyzing a T wave alternans is the temporal field analysis technique (see Verrier R. et al., “Median Beat Analysis of T-Wave Alternans to Predict Arrhythmic Death after Myocardial Infarction: Results from the Autonomic Tone and Reflexes after Myocardial Infarction Study,” Circulation, 102, 18; 2000: II-713 (abstract)). This method concerns calculating, for alternating beats, two averages of the T wave amplitudes at a given point of the repolarization segment and quantifying the difference in amplitude between the two averages.
Another known technique for analyzing a T wave alternans is the stretching technique (see U.S. Pat. No. 5,560,638 and Berger R. et al., “Beat-to-Beat QT Interval Variability: Novel Evidence for Repolarization Ability in Ischemic and Non-Ischemic Dilated Cardiomyopathy,” Circulation 1997; 96: 1557–1565). In this technique, one superimposes the T wave with a template and the temporal component is stretched so as to minimize the difference between the template and the analyzed beat.
Another known technique for analyzing a T wave alternans is the cross-correlation technique (see Burratini L. et al., “Computer Detection of Non-Stationary T-Wave Alternans Using New Correlative Method,” Computers in Cardiology 1997; 42: 657–660). This technique concerns quantifying, in the temporal field, the variations of amplitude and morphology (shape) of the repolarization wave on the basis of a correlation index; each T wave is correlated with a T wave average representative of a series of beats, an alternans, positive or negative, resulting in an oscillation of the correlation index around the median value.
Another known technique for analyzing a T wave alternans is the wavelets approach (see Couderc JP et al., “Beat-to-Beat Repolarization Variability in Patient LQTS with the SCN5A Sodium Channel Gene Mutation,” PACE, 1999, 22, 1581–1592). The ECG signal is broken up into a Gaussian sum and then processed so as to isolate the various complex components from the wave (P, QRS and T) so as to reveal singularities, and in particular an alternans for the T wave.